Exploring innovative treatments for non-healing diabetic foot ulcers through cutting-edge randomized controlled trials
Diabetic foot ulcers (DFUs) represent a significant global health challenge, affecting millions of individuals with diabetes, particularly those with type 2 diabetes mellitus (T2DM). These ulcers often result from a combination of peripheral neuropathy, peripheral arterial disease, and structural foot deformities. These conditions are frequently exacerbated by factors such as inappropriate footwear and unrecognized minor trauma.
Despite standardized management strategies, including serial sharp debridement, biomechanical offloading, and infection control, the healing outcomes for DFUs remain suboptimal. The financial burden of DFU treatment is significant, with healthcare expenditures in the United States alone exceeding $38 million annually. Furthermore, individuals from low-income or underserved populations often face substantial barriers to accessing advanced wound care services.
PURION-processed lyophilized human amnion/chorion membrane (ppLHACM) products, such as EPIEFFECT and EPIXPRESS, have shown significant promise in the treatment of chronic, non-healing wounds. These biologically derived allografts are known for their anti-inflammatory, antimicrobial, antifibrotic, and pro-epithelialization properties, making them a compelling therapeutic option for DFUs.
The processing method preserves the extracellular matrix (ECM) components and sterilizes the graft, ensuring that each layer is adequately cleansed before forming the tri-layer configuration. This meticulous process enhances the regenerative potential of these products, supporting tissue regeneration and promoting wound healing.
The novel modified platform trial design employed in this study represents a significant advancement in wound care research. Unlike conventional randomized controlled trials, which are typically limited in scope and time, platform trials incorporate adaptive features that allow for the addition or discontinuation of study arms based on pre-defined interim analyses.
This flexibility supports real-time decision-making and improves trial efficiency by sharing infrastructure, control arms, and statistical frameworks across multiple investigational products. The adaptive platform structure permits the introduction of additional ppLHACM or advanced wound care products through protocol amendments, ensuring that the trial remains scientifically rigorous and clinically relevant as new evidence and technologies emerge.
The primary objective of this study is to evaluate the efficacy of ppLHACM products in achieving complete wound closure within 12 weeks when used in conjunction with standard of care (SOC) compared to SOC alone. Secondary objectives include determining the time to closure, percentage area reduction, the frequency and nature of adverse events, and quality of life assessments.
The trial is a multicenter, prospective, randomized controlled trial utilizing a modified platform design. Patients with non-healing DFUs are randomized into three groups: SOC alone or SOC plus one of two ppLHACM products. Exploratory objectives include assessing offloading compliance, bacterial load, host protease activity, and continuous glucose monitoring data. The study is anticipated to require 24 months to complete, with up to 30 SerenaGroup or affiliated sites included.
This trial is expected to provide high-quality efficacy data on ppLHACM products, contributing to evidence-based practice in DFU management. The integration of continuous glucose monitoring (CGM) technology represents an innovative advancement, allowing for real-time, dynamic tracking of interstitial glucose levels, which can provide a more granular understanding of glycemic control and its impact on wound healing.
The successful implementation of this trial may serve as a model for future investigations in regenerative medicine, supporting the evolution of more responsive, efficient, and evidence-based approaches to chronic wound management. Future research may expand on this platform to include additional product classes, explore subgroup analyses based on wound characteristics or patient risk profiles, and incorporate emerging digital technologies for wound monitoring.